Leishmania amazonensis: multidrug resistance in vinblastine-resistant promastigotes is associated with rhodamine 123 efflux, DNA amplification, and RNA overexpression of a Leishmania mdr1 gene.
Exp Parasitol
; 81(4): 480-90, 1995 Dec.
Article
em En
| MEDLINE
| ID: mdl-8542989
ABSTRACT
A vinblastine-resistant Leishmania amazonensis cell line (RV100) which exhibits cross-resistance to the unrelated drug adriamycin, and thus is considered to be multidrug resistant (MDR), was isolated after stepwise selection with increasing concentrations of vinblastine. This phenotype was partially reverted by the calcium channel antagonist verapamil. Drug transport studies using the hydrophobic fluorescent dye rhodamine 123 demonstrated that the MDR cell line has a reduced dye accumulation due to an increased efflux. Furthermore, DNA and RNA hybridization studies demonstrated that a gene (lamdr1), homologous to ldmdr1 and lemdr1, was overexpressed and amplified within 27 kb extrachromosomal DNA circles (V-circles) in these cells. An independent cell line, RA5000, which was selected for resistance to adriamycin and was not cross-resistant to vinblastine, accumulated normal levels of rhodamine 123 and did not contain amplified DNA or overexpressed RNA of mdr-related sequences.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vimblastina
/
Verapamil
/
Doxorrubicina
/
Resistência a Múltiplos Medicamentos
/
Leishmania
/
Antiprotozoários
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Exp Parasitol
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Brasil